Fall In Hb Research Articles

Is there an association between low dose aspirin and anemia (without overt bleeding)? Narrative review.

BackgroundOvert bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, although this is known to occur in healthy volunteers. LDA is used increasingly in primary and secondary prevention of a number of medical conditions, many of which are common in older people, as is anemia. Anemia in older people is associated with adverse outcomes including disability, morbidity and mortality. The purpose of this study was to review the evidence that LDA might cause anemia without overt bleeding.MethodsAn extensive narrative review was carried out. Electronic searching (including database links) and reference lists of reports were used to identify studies reporting on use of aspirin ≤325 mg/day and anemia or change in hemoglobin (Hb) without overt bleeding. Data were extracted from reports of trials, adverse drug reactions (ADRs) and prevalence studies of adults aged ≥18 years, published since 1980.ResultsThere are few relevant data, with considerable heterogeneity among trial designs, duration, and patient characteristics in studies of LDA. In five randomised trials (n = 5879) in (mostly secondary) prevention, the majority of patients were men without peptic ulcer disease aged 50-70 years and no consistent association between LDA and change in Hb was found. In two smaller studies (n = 609) of primary prevention in healthy patients aged ≥70 years, there was a small but statistically significant fall in Hb with LDA. Observational studies, and data from trials in which use of LDA was not a primary focus of the study, were inconclusive.ConclusionsIt is not clear whether there is an association between LDA and anemia in the absence of overt bleeding, but there may be an association between LDA and fall in Hb in (a subset of) older patients. The available evidence has significant limitations, which are discussed; studies including more older patients, and publication of individual patient data, would help clarify this important matter.

Measures of blood loss and red cell transfusion targets for caesarean delivery complicated by placenta praevia

The objective of this study was to assess the association between transfusion, per cent drop in haemoglobin (Hb), and estimated blood loss during the delivery and the first postoperative week following caesarean delivery for placenta praevia. Clinical data predictive of an objective laboratory test for risk of haemorrhage and the need for transfusion were investigated. Transfusions outside national Guidelines were noted. Retrospective observational study of patients with placenta praevia, who were delivered consecutively by caesarean section at Royal Brisbane and Women's Hospital from 1999 to 2005. University-affiliated tertiary hospital. All caesareans were performed by one or more consultant obstetricians, gynaecology oncology surgeons and registrar assistants. Seventy-one (28.9%) of 246 patients with placenta praevia were transfused, with 45 of these receiving three or more red cell units. The antenatal Hb fell by a mean of 20.2% (SD 13.5). The average operative haemorrhage was estimated as 1225 mL (SD 996). No patient or surgical factors were significantly associated with changes in Hb. There was a significant association between per cent fall in antenatal Hb and both transfusion P < 0.001 and estimated loss P = 0.002. After transfusion, the Hb of 19 patients was higher than that recommended by Guidelines. Whether transfusion is necessary, but not the number of red cell units, can be planned by the effect of haemorrhage on antenatal Hb during delivery by caesarean section complicated by placenta praevia.

Reviewing the blood ordering schedule for elective orthopedic surgeries at a level one trauma care center

Background:Patients undergoing elective orthopedic surgeries often incur excess blood loss necessitating transfusion. The preoperative placement of blood requests frequently overshoots the actual need resulting in unnecessary crossmatching.Aims:Our primary goal was to audit the blood utilization in elective orthopedic surgeries in our hospital over a 1-year period and recommend a blood ordering schedule.Materials and Methods:A retrospective analysis of patients who underwent elective orthopedic surgeries over a period of 1 year was done. The data collected include patients’ age, sex, type of surgical procedure, pre- and postoperative hemoglobin (Hb) levels, number of units crossmatched, returned, transfused, crossmatch to transfusion ratio (C:T), transfusion indices, estimated blood loss for each surgical procedure, and the actual and predicted fall in Hb. We propose a blood ordering schedule based on surgical blood ordering equation.Results and Conclusions:A total of 487 patients with a median age of 37±17 years (mean ± standard deviation) were evaluated. One thousand three hundred and seventy-seven units of blood were crossmatched and only 564 units were transfused to 260 patients. Fifty-nine percent of the units crossmatched were not transfused. Six of the 12 elective procedures had a C:T ratio higher than 2.5. Ten of the 12 procedures (83.3%) had a low transfusion index (TI < 0.5). The calculated red blood cell units were less than 0.5 in 5 of the 12 elective procedures, and hence we recommend a group and save policy for these procedures. Blood ordering schedule based on patient and surgical variables would provide an efficient way of blood utilization and management of resources.

Maintenance of elevated versus physiological iron indices in non-anaemic patients with chronic kidney disease: a randomized controlled trial

An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD). One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment. Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups. Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L.

The effect of blood donation frequency on iron status

Introduction The effects of blood donation on iron status in donors without iron supplementation were studied. Analysing interactions between donations and iron status markers may predict these effects. Materials and methods Haemoglobin (Hb) and serum ferritin were analysed in 893 donors over 1 year. Serum transferrin receptor (sTfR) was measured at the first and last donation. Results Prolonged intervals prevented decrease in Hb in women and in ferritin for both genders. In women, a high TfR-F index (sTfR/log ferritin) predicted fall in Hb. Conclusion Adjusting the donation intervals is a way to prevent iron deficiency in blood donors.

Relationship Between Hemoglobin Concentrations and Outcomes Across Subgroups of Patients with Aneurysmal Subarachnoid Hemorrhage

Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4-5 vs. 1-3; modified Fisher score (MFS) 4 vs. 0-3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6-11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (beta = -0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients.

Double-balloon enteroscopy for small-bowel polyps treatment in patients with Peutz-Jeghers syndrome

AIM:To assess the usefulness of double-balloon enteroscopy (DBE) for the detection and treatment of small-bowel polyps in patients with Peutz-Jeghers syndrome. METHODS:We performed a prospective evalu-ation of patients with clinically proved Peutz-Jeghers syndrome who were enrolled in DBE surveillance and treatment program. The size, number of the endoscopically resected small-bowel polyps, and the complications associated with the examination or treatment were docu-mented. RESULTS:Thirty-four DBE procedures were carried out in 18 patients (oral approach in 18, anal approach in 16). The mean duration of theprocedure was 95 (range 65-180) min. Small-bowel polyps were detected in all patients (100%). A total of 126 polyps (diameter 5-10 mm, 16 polyps; 11-30 mm:70 polyps; 30 mm:40 polyps; the largest diameter:50 mm) were resected endoscopically. One carcinomatous change of polyp was noted. A total of three complications occurred (1 perforation occurred 3 days after endoscopic resection, 2 abdominal pains, non-bleeding with a fall in Hb), and no other severe complications occurred. CONCLUSION:DBE is a safe and reliable proce-dure for the treatment of mid-small bowel pol-yps in patients with Peutz-Jeghers syndrome. It revolutionizes the therapeutic options for polyps in the region of the mid-small bowel and limits the indications for primary surgical manage-ment.

Diagnostik und Therapie von Dünndarmpolypen mittels Push-and-Pull-Enteroskopie in Doppelballontechnik bei Patienten mit Peutz-Jeghers-Syndrom

Peutz-Jeghers syndrome (PJS) is characterised by a combination of hamartomatous gastrointestinal polyps and mucocutaneous melanin pigmentation. The polyps occur mainly in the small bowel and can lead to intestinal obstruction, intussusception and bleeding. Until only a few years ago, primary surgical resection and intraoperative endoscopy and polypectomy were the only available means of treating polyps in the mid-small bowel in these patients. With the introduction of double-balloon enteroscopy (DBE), we now have not only an improved diagnostic tool but also a non-surgical treatment option. Between March 2003 and September 2006 a total of 16 patients with PJS were examined by DBE and treated endoscopically. The size, number and location of the diagnosed and endoscopically resected small-bowel polyps were documented as were all complications associated with the examination or treatment. A total of 47 DBE-procedures were performed (oral approach 39, anal approach 8). The examinations revealed a total of 178 polyps. 47 polyps were removed by endoscopic polypectomy on the grounds of their size and/or gross appearance. The largest small-bowel polyp resected was 50 mm (min. 15 mm, max. 50 mm). A total of four complications occurred (2 episodes of bleeding with a fall in Hb, 1 perforation, 1 propofol-associated decrease in oxygen saturation). DBE is a safe and reliable procedure for the diagnosis of small-bowel polyps in patients with PJS. In addition to macroscopic assessment and biopsy of suspicious areas, it permits the exact localisation as well as preoperative marking of polyps that are primary candidates for surgery. DBE revolutionises the therapeutic options for polyps in the region of the mid-small bowel and limits the indications for primary surgical management.

Peutz-Jeghers Syndrome: Endoscopic Detection and Treatment of Small-Bowel Polyps By Double-Balloon Enteroscopy

Introduction: Peutz-Jeghers Syndrome (PJS) is characterized by a combination of hamartomatous gastrointestinal polyps and mucocutaneous melanin pigmentation. The polyps occur mainly in the small bowel and can lead to intestinal obstruction, intussusception and bleeding. Until only a few years ago, primary surgical resection and intraoperative endoscopy and polypectomy were the only available means of treating polyps in the mid-small bowel in these patients. With the introduction of double-balloon enteroscopy (DBE) we now have not only an improved diagnostic tool but also a non-invasive treatment option. Methods: Between 03/03 and 06/06 a total of 16 patients (m: 9, mean age: 35 years) with PJS were examined once or more by DBE with oral and/or anal insertion and treated endoscopically. The size, number and location of the diagnosed and endoscopically resected small-bowel polyps were documented as were all complications associated with the examination or treatment. Results: A total of 37 procedures were performed (oral approach: 33, anal approach: 4). The examinations revealed a total of 55 polyps measuring more than 10 mm (max. 50 mm) and 112 polyps measuring 10 mm or less. Thirty-four polyps were removed by endoscopic polypectomy on the grounds of their size and/or gross appearance. The largest small-bowel polyp resected was 50 mm (mean: 24 mm, range: 10-50 mm). The histological work-up of the specimens revealed focal high-grade intraepithelial neoplasia in one patient. A total of four complications occurred in two patients (two episodes of bleeding with a fall in Hb, one perforation, one propofol-associated decrease in oxygen saturation). Conclusion: DBE is a safe and reliable procedure for the diagnosis of small-bowel polyps in patients with PJS. In addition to macroscopic assessment and biopsy of suspicious areas it permits exact localization as well as preoperative marking of polyps which are primary candidates for surgery. DBE revolutionizes the therapeutic options for polyps in the region of the mid-small bowel and limits the indications for primary surgical management. The aim is early detection of the polyps and their timely endoscopic resection (polyp size < 30 mm). Primary surgical management is only indicated in the case of very large and/or sessile polyps which cannot be resected endoscopically, suspected invasive cancerous growth, endoscopic inaccessibility and acute emergencies (acute gastrointestinal bleeding, mechanical ileus, intussusception).

Haemoglobin levels following unicompartmental knee arthroplasty: Influence of transfusion practice and surgical approach

A retrospective review was undertaken of preoperative and day 3 postoperative haemoglobin (Hb) levels in all unicompartmental knee arthroplasty (UKA) procedures performed by a single surgeon. Sixty-six UKAs were performed using the same prosthesis through an open approach with patella eversion. This group was compared with 212 UKAs performed using a minimally invasive approach without patella eversion, with an implant and instrumentation specifically devised for this approach. Both groups were well matched for patient demographics, surgical and anaesthetic techniques, thromboprophylaxis, and postoperative regimes. All patients received transfusions with pre-donated blood, except the unilateral minimally invasive approach group. An analysis of covariance was undertaken to examine the influence of the surgical approach and whether surgery was unilateral or bilateral, taking into account preoperative Hb levels and units of blood transfused. The average fall in Hb following UKA, adjusted for other variables, was 2.73 g/dl with an open approach compared to 1.82 g/dl with a minimally invasive approach. This difference was significant ( p=0.0044). The average postoperative Hb in the minimally invasive group was 12.05 g/dl (range, 8.8 to15.8 g/dl). Patients undergoing unilateral minimally invasive UKA are unlikely to develop symptomatic anaemia and should not be required to predonate blood or undergo transfusion.

The Natural History of Mutated, Stage AO Chronic Lymphocytic Leukemia.

Patients who present with stage AO CLL and have mutated IgVH genes are generally considered to represent a benign sub-set of CLL with prolonged survival .However, within this subgroup there is considerable heterogeneity with regard to disease progression and the need for treatment. From a cohort of 260 patients studied at a single centre, we identified 70 who presented with stage AO disease as an incidental finding on a routine blood count and who had mutated IgVH genes. 47 were followed up for over 10 years without receiving treatment. 31/47 remained stage AO with a lymphocyte count of <20 x 109/l and were considered to have stable disease (SD). 16/41 remained Stage A with a gradually rising lymphocyte count and were designated as having slowly progressive disease (SPD). 23/70 had progressive disease (PD), defined by one or more of the following parameters: an increase in stage, the appearance of lymphadenopathy > 1cm or splenomegaly, a persistent fall in Hb or platelet count, LDT of <1 year or the need for treatment. There was no difference in mean ZAP 70 expression, CD38 expression using 7% and 30% cut-off's, % of IgVH gene mutations, IgVH gene usage, p2 X7 polymorphisms or presenting serum immunoglobulin levels among the three subgroups. Gene expression profiling using the lymphochip microarray was performed on 14 cases with PD, 8 with SPD and 12 with SD. No significant differences in gene expression were found. Karyotypic abnormalities at presentation were found in 68% of patients with PD, 31% with SPD and 27% SD (p= 0.007). The most frequent abnormality was (t)/del 13q14, found in 43%,0% and 16% of patients with PD, SPD and SD respectively. When interphase FISH and Southern analysis were also used to detect del13q14, the incidence of loss in the 3 groups rose to 91%,68% and 70% respectively, indicating both the high frequency of 13q loss and the greater responsiveness of leukemic cells to mitogens in patients destined to have PD. Loss of the ATM or p53 genes were found at presentation or on sequential testing in 4 patients with PD but not in SPD or SD. Patients with SD and SPD remained asymptomatic on prolonged follow-up and were not prone to recurrent infections. In contrast, 12 patients with PD had recurrent infections and 8 received regular immunoglobulin infusions. There was no significant difference between serum IgG, IgA and IgM levels between patients with PD and those with SPD or SD at presentation. However serum IgG but not IgA or IgM levels were significantly lower on follow-up in patients with PD compared to SPD and SD (p <0.0001). A subset of patients with good prognosis CLL develop progressive disease which is associated with significant morbidity due to immuno-deficiency. Apart from differences in the frequency of cytogenetic abnormalities, these patients are not readily identified at presentation using currently available prognostic markers.

Utilisation of the Rockall Score in the Development of a Clinical Pathway for the Management of Non-Variceal Upper Gastrointestinal Bleeding

Background: The Rockall scoring system (based upon co-morbidities, haemodynamic stability and endoscopic appearances) has been validated to predict outcome from non-variceal upper GI bleeding. We believed that the post-endoscopy Rockall score could be used to determine a length of stay recommended by a clinical pathway for non-variceal upper GI bleeding. Methods: Patients presenting with a upper GI bleeding were admitted to high dependency (HDU) or the gastroenterology ward depending upon their pre-endoscopy Rockall score. After endoscopy they were assigned a post-endoscopy Rockall score. Patients with a post-endoscopy Rockall score of greater than 7 (or who had required endoscopic therapy) were managed initially in HDU, with an expectation of discharge to the ward in 36 hours, those less than 7 were admitted to the ward with an aim for discharge within 48hrs. Endoscopic high risk lesions were treated with adrenalin injection +/- argon plasma coagulation followed by PPI infusion. Non-parametric, two-tailed Spearman coefficient calculation was used to determine the correlation between Rockall score and length of stay (total and HDU) and transfusion rates. Results: 165 patients (mean age 65.1, r:15-94 years) were entered over 10 months. Total length of stay, HDU stay and transfusion rates correlated with post-Rockall score (r=0.313, p<0.01:r=0.186, p<0.02:r=0.308, p<0.01). Patients with a post endoscopy Rockall score between 1-2 had a mean total length of stay of 2.8 days (and 0.92 units transfused), compared with 4.2 days (1.8 units) and 4.3 days (2.8 units) respectively for those with scores between 3-4 and greater than 5. Significant rebleeds (defined by a 20g/L fall in Hb) occured in 14 of all patients (8.4%), with 10 of these in the 45 (22%) patients with pepic ulcer disease. Three of the bleeding peptic ulcers (6%) proceeded to surgery, with one death (2.2%) due to an acute MI. There were 3 other deaths (2 due to presumed acute myocardial infarction (AMI) prior to endoscopyand 1 from sepsis) leading to an overall mortality of 2.4%. Discussion:We have demonstrated that the post endoscopy Rockall score predicts total and HDU legth of stay, as well as transfusion requirements.This enables us to predict expected length of stay in the patients clinical pathway immediately following their endoscopy for non-variceal upper GI bleeding. This will enable the easier detection of variance from the clinical pathway with respect to length of stay.

Delayed hemolytic transfusion reaction/hyperhemolysis syndrome in children with sickle cell disease.

Alloimmunization in patients with sickle cell disease (SCD) has a reported incidence of 5% to 36%. One complication of alloimmunization is delayed hemolytic transfusion reaction/hyperhemolysis (DHTR/H) syndrome, which has a reported incidence of 11%. In patients with SCD, clinical findings in DHTR/H syndrome occur approximately 1 week after the red blood cell (RBC) transfusion and include the onset of increased hemolysis associated with pain and profound anemia. The hemoglobin (Hb) often drops below pretransfusion levels. In many reported adult cases, the direct antiglobulin test (DAT) remains negative and no new alloantibody is detected as the cause for these transfusion reactions. To date, few pediatric cases have been reported with this phenomenon. The objective of this study was to describe the clinical and laboratory findings of a case series in children who had SCD and experienced a DHTR/H syndrome at our institution. An 11-year retrospective chart review of patients with discharge diagnosis of SCD and transfusion reaction was performed. DHTR/H syndrome was defined as the abrupt onset of signs and symptoms of accelerated hemolysis evidenced by an unexplained fall in Hb, elevated lactic dehydrogenase, elevated bilirubin above baseline, and hemoglobinuria, all occurring between 4 and 10 days after an RBC transfusion. Patient characteristics, time from transfusion, symptoms, reported DAT, new autoantibody or alloantibody formation, laboratory abnormalities, and complications were recorded. Patients with acute transfusion reactions were excluded. We encountered 7 patients who developed 9 episodes of DHTR/H syndrome occurring 6 to 10 days after RBC transfusion. Each presented with fever and hemoglobinuria. All but 1 patient experienced pain initially ascribed to vaso-occlusive crisis. The DAT was positive in only 2 of the 9 episodes. The presenting Hb was lower than pretransfusion levels in 8 of the 9 events. Severe complications were observed after the onset of DHTR/H: acute chest syndrome, n = 3; pancreatitis, n = 1; congestive heart failure, n = 1; and acute renal failure, n = 1. DHTR/H syndrome occurs in pediatric SCD patients, typically 1 week posttransfusion, and presents with back, leg, or abdominal pain; fever; and hemoglobinuria that may mimic pain crisis. Hb is often lower than it was at the time of original transfusion, suggesting the hemolysis of the patient's own RBCs in addition to hemolysis of the transfused RBCs; a negative DAT and reticulocytopenia are often present. Severe complications including acute chest syndrome, congestive heart failure, pancreatitis, and acute renal failure were associated with DHTR/H syndrome in our patients. DHTR/H in the pediatric sickle cell population is a serious and potentially life-threatening complication of RBC transfusion. It is important to avoid additional transfusions in these patients, if possible, because these may exacerbate the hemolysis and worsen the degree of anemia. DHTR/H syndrome must be included in the differential of a patient who has SCD and vaso-occlusive crisis who has recently had a transfusion.

Chronic Toxicity Study Of The Effect Of Crude Petroleum (Bonny Light), Kerosine And Gasoline On Rats Using Haematological Parameters

Haematological parameters such as haemoglobin content (Hb), pack cell volume (PCV) and white Blood Cell Counts (WBC) were used to assess the effect of crude oil (bony light), kerosene and gasoline on rats chronically exposed to 15kg-1,7.5kg-1 and 5gk-1 of the respective petroleum samples of crude petroleum (bony light), kerosene and gasoline. These samples were administered intraperitoneally and monitored for first, second and third months of exposure. A significant fall in Hb and PCV were observed in the three sample groups through the 3 months duration. For gasoline injected rats the Hb decreased from 13.86 0.21 of control to 6.35 0.49 at third month, kerosene from 13.860.21 of control to 9.18 2.80 and crude petroleum (bonny light) from 13.86 0.21 of control to 10.67 0.65 at third month. Furthermore, the PCV decreased from 41.50 0.71 of control to 19.051.47 at the third month for gasoline, kerosene decreased from 41.50 0.71 of control to 27.748.40 at the third month, with crude petroleum (bonny light) decreasing from 41.50 0.71 of control to 31.91 1.95 at the third month. Finally the WBC seemed to increase marginally from 4.65 0.07 of control to 5.00 0.14 at the third month with gasoline, 6.85 1 1.39 at third month with crude petroleum (bony light) . in conclusion, the results seemed to suggest that long term exposure of rats to petroleum samples could induce anaemia through the reduction in Hb and PCV levels as obtained in this study. (Journal of Applied Sciences & Environmental Management: 2002 6(1): 60-63)

The Effect of Fetal Hydrops on the Rate of Fall of Hemoglobin after Fetal Intravascular Transfusion for Red Cell Alloimmunization

Objective: We aimed to assess whether there is a difference between hydropic and nonhydropic fetuses in the rate of fall of hemoglobin (Hb) following intravascular transfusions. Methods: Eighty-three intravascular transfusions in 34 fetuses were analyzed. The pretransfusion and posttransfusion Hb values, the gestational age, the volume of blood transfused, the number of days between transfusions and the rate of fall of Hb per day following a transfusion were assessed. Hb levels were expressed as multiples of standard deviation from the normal mean for gestational age. Results: Eleven fetuses were hydropic at presentation and 23 were not. Twenty-three transfusions were undertaken in the 11 fetuses while they were hydropic and 60 transfusions were performed in nonhydropic fetuses. Comparisons of transfusion variables between the two groups were performed both for the first transfusion only and also for the total number of transfusions. The rate of Hb fall per day following a transfusion was similar in the two groups on both comparisons. The posttransfusion Hb level tended to be lower and the intervals between transfusions were a little shorter in the hydropic group, but these differences were not statistically significant. Conclusion: The posttransfusion Hb tended to be lower in the hydropic fetuses, but the fall in Hb was not faster in these cases. Therefore, with a similar rate of daily Hb decline in both groups, the hydropic fetuses are expected to become anemic again sooner than the nonhydropic fetuses only because of the lower posttransfusion Hb. The timing of the next transfusion should therefore be based on the posttransfusion Hb and the normal predicted drop per day irrespective of the presence or absence of hydrops.

Effects of acute iron overload on Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss).

Distribution of radioiron to various tissues after intraperitoneal injections was examined in Atlantic salmon and rainbow trout. Liver and spleen were found to be the major iron storage tissues. Injections of 1 or 5 mg iron as ferric ammonium citrate led to a fall in hemoglobin levels in both species after 2 d. Hemoglobin levels returned to normal levels in rainbow trout after 8 d, but Atlantic salmon had not recovered, and Hb levels fell below 3 g/100 mL. In both species, the fall in Hb was associated with a raise in iron levels in spleen and liver, suggesting damage to erythrocytes. Atlantic salmon liver ferritin showed a two- to threefold increase, while rainbow trout showed a sixfold increase, and a more rapid response. The toxic effect of iron in fish appears to be different from the effect in other vertebrates.

ROLE OF ALLOPURINOL IN REDUCING CEREBRAL HVPOXIC-ISCHEMIC INJURY DURING REOXYGENATION-REPERFUSION

Oxidation of hypoxanthine (HX) by xanthine oxidase (XO) has been hypothesized to be a potential source of oxygen-derived free radicles (O2−) during reoxygenation-perfusion of hypoxic-ischemic organs. Allopurinol (Al), a XO inhibitor, can reduce reperfusion injury. During hypoxia-ischemia, components of the mitochondrial electron-transport chain become reduced. With reoxygenation-reperfusion O2− are generated. A Near Infrared Spectroscope (Niroscope) was used to continuously monitor changes in cytochrome aa3 (Cytaa3), blood volume (BV), saturated Hb (HbO) and desaturated (HB-) in 24 rats. The rats were divided into 2 groups (Gp). Gp1 (12). Wt=286±38 g (m±SD) received Al (dose 200 mg/kg IP) and was subjected to 1/2 hr period of 9.7%O2 followed by 100%O2 GP2 (12). Wt=282±4lg (m±SD) was subjected to the same 2 periods of FiO2 but without prior Al Results: Gp1 With administration of 9.7% O2, Cytaa3 became more reduced, by as much as 100% of total labile signal (TLS), with concomitant fall in BV and HbO and rise in Hb. With administration of 100% O2, Cytaa3 became more oxidized with concomitant rise in BV and HbO and fall in Hb. Gp2. During the hypoxic period (9.7%O2) the changes in Cytaa3, BV, HbO and Hb- were similar to those obtained in Gp1. However on reoxygenation with 100% O2 the Cytaa3 remained reduced despite increases in BV and HbO and fall in Hb-. To evaluate the role of HX and XO in these changes, an additional 6 rats on 100% O2 were infused with I. HX (dose calculated 10 provide a plasma concentration 30 μM/dl). 2.HX with Arabinose (dose 2-4 ml of 1.6 M Sol.) 3. HX + XO (I unit) Infusion of HX, and XO, with or without arabinose, did not result in any change in cytaa3 Our results suggest that allopurinol protect the mitochondrial electron-transport chain from O2− during reoxygenation-reperfusion following cerebral hypoxic-ischemic injury probably by scavenging O2− rather than by inhibition of xanthine oxidase.

Iron status markers in patients with small cell carcinoma of the lung. Relation to survival.

A longitudinal study of iron status markers (haemoglobin (Hb), serum (S-) iron, S-transferrin, transferrin saturation, S-ferritin) was performed in 31 chemotherapy treated patients with small cell lung cancer. At discovery, eight patients were anaemic (Hb less than 121 g l-1). Hb, S-iron and transferrin saturation were lower (P less than 0.01), and S-ferritin higher (P less than 0.01) than in healthy subjects. Chemotherapy induced an immediate fall in Hb (P less than 0.003), increase in S-iron (P less than 0.003) and transferrin saturation (P less than 0.001). Later in the disease a fall in S-transferrin (P less than 0.006) and an increase in S-ferritin (P less than 0.02) occurred. Thirty patients died during the 2 years observation. S-ferritin at discovery was correlated to performance status score (r = 0.57, P = 0.01) and to survival (r = -0.63, P less than 0.0002). Patients with S-ferritin less than or equal to 400 micrograms l-1 (n = 13) had longer survival than those with S-ferritin greater than 400 micrograms l-1 (n = 18) (P = 0.004).

Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anaemia for stimulation.

Serum erythropoietin (Epo) was measured in 23 patients before, during and after intensive cytostatic treatment courses for acute leukaemia or before bone marrow transplantation. A marked increase was seen in all patients, starting 1 or 2 d after initiation of treatment. A peak was reached after about 7 d, at levels as high as 1450 IU/l, after which Epo fell rapidly, even in patients who were anaemic at that time. In 13 of the patients there was no fall in Hb level that could explain the increase in Epo. The increase was too large to be explained by an altered Epo metabolism or marrow utilization. Cytostatic drugs cause an increase in Epo production not mediated through anaemia, possibly initiated by a cytostatic effect on the kidneys or by an unknown stimulatory factor, responsive to bone marrow inhibition.

Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer

Sixty patients with FIGO stage IIb, IIc, III and IV ovarian cancer were entered into a randomized Phase III study of cyclophosphamide 600 mg/m 2 with cisplatin 100 mg/m 2 , iproplatin 240 mg/m 2 or carboplatin 300 mg/m 2 . Dose modifications were made according to renal function and myelotoxicity. The arms containing carboplatin (CBDCA) and iproplatin (CHIP) were not shown to be significantly different from the cisplatin containing arm with regard to response rate, duration of response and survival. Subjective toxicity showed that cisplatin and cyclophosphamide therapy was associated with more nausea and vomiting ( P = 0.0005). The duration of vomiting showed a significant increase with successive courses of chemotherapy for the cisplatin containing arm only ( P < 0.003). The cyclophosphamide/CHIP combination caused significantly more diarrhoea ( P < 0.0006). Alopecia was more severe ( P < 0.02), and neurotoxicity was more common, in patients who received cyclophosphamide and cisplatin (paraesthesiae P = 0.0007, tinnitus P < 0.00005, deafness P = 0.0018). All three combinations caused cumulative toxicity on haemoglobin (Hb) ( P < 0.001 for each treatment), leukocyte count (WCC) ( P < 0.0005 for each treatment), and platelet count ( P < 0.0005 for each treatment). The degree of fall in Hb for each course of therapy was greater in the cisplatin containing arm compared with the CHIP and CBDCA arms which were not significantly different from each other ( P = 0.0005). For WCC the cisplatin/cyclophosphamide regimen was significantly less toxic than CHIP/cyclophosphamide, with CBDCA/cyclophosphamide falling between the two and not being significantly different from either ( P = 0.0005). The CHIP containing arm caused more thrombocytopenia than the other arms which were of equal toxicity ( P < 0.0005). Serum creatinine showed a gradual significant overall rise with each course of cisplatin/cyclophosphamide therapy ( P < 0.0005), whereas the CBDCA arm showed no change and the CHIP arm showed a small fall in serum creatinine after most courses of therapy. This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. The CHIP/cyclophosphamide regimen caused more thrombocytopenia and diarrhoea. The CHIP and CBDCA containing arms caused more leukopenia than the cisplatin containing regimen. Either iproplatin or carboplatin would be an acceptable alternative to cisplatin in chemotherapy regimens, and would result in reduced toxicity.